NANOTOES Résumé de rapport

The ITN NanoTOES has addressed the need for training of experts in nanomaterial safety. The development of nanotechnology has resulted in the use of nanomaterials in a wide variety of applications. Nanoenabled products are produced and applied to create advantageous product properties which could not be obtained with conventional materials. The rapid development of the field has resulted in a situation in which many different kinds of nanomaterials are increasingly present at the work place, in consumer products and – post consumption – in the environment. It is necessary to assess potential risks deriving from these novel compounds in order to ensure safety for health and environment. This requires a highly interdisciplinary competence and experts for nanosafety are urgently needed. Indeed, data obtained within the on-going FP7 CSA NanoEIS show that industry expresses a substantial need to recruit people with expertise in health, safety, regulation and the environment. Ideally, such nanosafety experts should have an extremely wide range of competences, covering e.g. technical, biological, medical, environmental and legal aspects. This is clearly an unrealistic expectation, but it is possible to educate experts that are highly competent in one or more of the relevant fields, and have at the same time a good understanding of adjacent areas, as well as an established network of colleagues who can be consulted for specific issues. So far, there is no “gold standard” for training of such specialists. NanoTOES has developed a reference model for training of PhD students and postdocs in nanosafety research, which can in the future be used to plan similar training efforts. The 13 fellows working in 12 European institutions which have been trained in NanoTOES are thus in a good situation to meet existing needs and become leaders of the field in the future.All the fellows have worked on individual research projects, mostly within PhD programs. NanoTOES has ensured strong linking between the fellows, which has fostered networking and team spirit, but also provided the interdisciplinary and trans-sectoral approach which is necessary for successful work. The main tools for active project work were:1) Biannual meetings, during which all fellows presented and discussed the status of their work. In addition, external experts gave talks on relevant issues, for example ethics in science, entrepreneurship, patenting of nanomaterials, risk communication, and presentation skills.2) All fellows spent time working in partner laboratories. These secondments typically lasted 2-6 weeks and focused on practical work. Care was taken to ensure that all fellows spent time both in academic and in industrial environments.3) The homepage and web platform (www.nanotoes.eu) is a major communication tool for quick exchange between fellows in different locations. It is also the showcase of the project where people interested in our work can find more information about our activities.NanoTOES started in November 2010 and finished its work in February 2015. The main outputs of the project are 13 highly competent fellows that are ready to move on to a successful career. So far, 21 publications have been published by the fellows, with 8 more submitted and a substantial number still in preparation. Along with numerous presentations at conferences, these activities have ensured that results from the project have been made available to the experts in the field. It is difficult to point out some works as especially important, but one can summarize general experiences made within the projects of the fellows.Are nanoparticles toxic? The answer is clearly yes, but as the physician Paracelsus famously stated in the 16th century, everything is toxic and it is only the dose that makes that something is not toxic. One recurring question was thus how the dose at which toxicity was observed in various biological test systems relates to the dose that can be reached via normal human exposure. The answer is not always simple, since it is not trivial to estimate e.g. work place exposure and often data on this are lacking. It is not even trivial to estimate the exposure in a test tube. To take one example, several studies have used human cells in which human lung or gut cells form a layer at the bottom of a cell culture vessel. A known concentration of nanoparticles is added, but the cells are only exposed to particles that directly contact them und not by those that float freely in the medium. The exposure is influenced by properties of the particles that change while they are in the cell culture medium. For example, they may dissolve, so cells are now exposed to the chemical components instead of particles. Alternatively, particles may agglomerate, which means that they sink much faster to the bottom. Taking those effects into account, the doses at which toxicity was observed were mostly much higher than those reached in realistic scenarios. Of note, there are two situations where much higher nanoparticle exposures may be reached: Accidents, in which the amount of particles can be huge, and medical applications, in which very high doses are applied, often directed to a single site, like a wound.A second major theme of essentially all projects was to understand molecular mechanisms of toxicity. This is a very important area of research, since a better understanding on which properties make a nanoparticle toxic will increase our ability to predict toxic effects. This knowledge can be used to consciously apply toxic agents, e.g. in medicine or as antibacterial agents. It also opens the route to develop nanoparticles that retain desired properties but lack those that would create hazards: A concept known as safety-by-design. Properties linked to toxicity that were identified in individual projects included particle size, shape, surface charge, attachment of specific chemicals on the surface, and release of toxic metal ions. In several cases toxicity was found to be due to unwanted contaminants, mainly bacterial compounds that act as pro-inflammatory stimuli on their own right, so the nanoparticles are only harmless carriers for them.The need to improve assays for such bacterial substances leads to the third major activity in which the fellows have been active: The development of new methods and the adaptation of existing ones to the conditions of nanoparticle exposure. Methods were developed addressing for example release of silver ions, changes that nanoparticles undergo when they get in contact with blood compounds, the production of highly reactive and thus toxic oxygen species induced by nanomaterials, the induction of inflammation, and both mutations and breakage of DNA, which may lead to cancer. In summary, the fellows have been successful in performing state-of-the-art research in this highly innovative field and they are now in an excellent position to build careers in nanotechnology, nanomedicine and other related areas. The ITN has given them a thorough and broad expertise as well as an established network of colleagues all over Europe. We shall watch their career developments with great expectations.Contact: Prof. Dr. Albert Duschl, NanoTOES coordinator, University of Salzburg, Austria, Phone 0043 662 8044 5731, e-mail albert.duschl@sbg.ac.at, website www.uni-salzburg.at/tapir. Project website: www.nanotoes.eu